I propose to write the first history of Anglo-America's most enduring popular medical book, Aristotle's Masterpiece. First published in London in 1684, the book became an instant success, and was still for sale in the early twentieth century. My analysis focuses upon readership to understand how and why the book appealed over such a long time span in both England and America. I argue that the book was both canonical, widely known to provide advice about sex and reproduction, but also flexible, tweaked by printers and publishers to adapt to changing markets. The Masterpiece in its various forms offers a rare window into plebian sexual cultures as well as rich evidence of ordinary people's interactions with the printed book. More generally, the project builds a model for investigating such vernacular knowledge, the basis of most health care until recently. Drawing upon the methods of cultural history, I argue that we need to understand how knowledge was circulated, consumed, and reproduced in changing contexts.